Conformational selection in artificial catalysts and molecular machines

Enzymes exist as a spontaneously interconverting ensemble of conformational states which likely enables their extremely high catalytic activity. Conformational selection proposes that the fastest reaction pathway samples different conformational states along the reaction coordinate, providing access to lower energy pathways otherwise inaccessible to any one conformation in isolation. This mechanical rate dependence is synonymous with information ratchet mechanisms, a process that drives every biological molecular machine. Although the impressive catalytic activities of enzymes have provided inspiration to chemists, the majority of artificial catalysts are designed to be static, a feature that may limit their catalytic potential. The introduction of dynamics to a catalyst can facilitate a ratchet mechanism allowing optimisation for opposing elemental steps thereby surpassing the static Sabatier limit.
In addition to using ratchet mechanisms to improve catalytic efficiency, biology utilises ratcheting to build complexity through anabolism.2 Anabolism transforms low energy building blocks into higher energy products, an endergonic process. This endergonic transformation is possible as it is coupled it to an orthogonal exergonic process, generally using ATP as the chemical fuel. In contrast, the majority of synthetic transformations are exergonic proceeding energetically downhill to either a local or global energy minimum. Light driven reactions provide an exception to this rule allowing a higher energy plane to be traversed by the reagents and proceeding explicitly through a ratchet type mechanism. However, such transformations are limited to those which can interact with light either directly or via a catalyst. Similarly, deracemizations have been achieved through chemical fuelling but this is limited exclusively to entropic work. Taking inspiration from biology, to expand these fuelled endergonic reactions to otherwise inaccessible bond forming reactions would greatly expand the chemists' toolbox.
Biology makes extensive use of ratchet mechanisms which contribute significantly to its efficiency. The implementation of these principles to synthetic catalysis, and synthesis more generally, has the potential to decrease both the cost and energy requirements whilst simultaneously expanding the chemical transformations available to the chemist.

iCAT will work with industry partners to create an holistic approach to the training of students in biocatalysis, chemocatalysis, and their process integration. Traditional graduate training typically focuses on one aspect of catalysis and this approach can severely restrict innovation and impact. Advances in technology and fundamental reaction discovery are rendering this silo-approach obsolete, and a new training modality is needed to produce the next generation of chemists and engineers who can operate across a far broader chemical continuum. iCAT will meet this challenge with a state-of-the-art CDT, equipping the next generation of scientists and engineers with the skills needed to develop future catalytic processes and create the functional molecules of tomorrow.

The UK has one of the world's top-performing chemical industries, achieving outstanding levels of growth, exports, productivity and international investment. The UK's chemical industry is a significant provider of jobs and creator of wealth, with a turnover in excess of £50 billion and a contribution of over £15 Billion of value to the UK economy [2015 figures]. iCAT will deliver highly skilled people to lead this industry across its various sectors, achieving impact through the following actions:

1. Equip the next generation of science and engineering leaders with the interdisciplinary skills and knowledge needed to work across the bio and chemo catalytic remit and build the functional molecules we need to structure society.

2. Provide a highly skilled workforce and research base, skilled in the latest methodologies, strategies and techniques of catalysis and engineering that is crucial for the UK's Chemical Industry.

3. Build the critical mass necessary to support effective cohort-based training in a world-class research environment.

4. Develop and disseminate new catalytic technologies and processes that will be taken up by industrial and academic teams around the world.

5. Encourage Industry to promote research challenges within the CDT that are of core relevance to their business.

6. Provide cohesion in the integration of biocatalysis, engineering and chemocatalysis to create a more unified voice for strategic dialogue with industry, funders and policy makers, and more generally outreach and public engagement.

7. Draw-in and bring together Industrial partners to facilitate future Industrial collaborations.

8. Benefit Industrial scientists through interactions with the CDT (e.g. training and supervisory experience, exposure to cutting-edge synthesis and catalysis etc).

9. Link with other activities in the landscape: bringing unique expertise in catalysis to, for example, externally-funded University-led initiatives, EPRSC Grand Challenge Networks, and the National Catalysis Hub.